IGHE and hemophilia A: Differently from ERT in hemophilia A, where detection of IgG4 is typically associated with presence of inhibitor23, 48, 49, the presence of increased levels of non-neutralizing IgG4 antibodies, in the absence of IgE antibodies, in treated LOPD subjects compared with HD and untreated LOPD subjects possibly reflects the desensitization to the immunogen24, 50, 51, 52.